The use of ultrasound contrast agents has become more popular in recent years. Many manufacturers currently have a variety of agents under development. Each ultrasound contrast agent responds differently when exposed to ultrasound energy, which can pose a problem if the ultrasound system is not aware of the agent being utilized. In addition, the concentration of the agent and its injection rate also affects the quality of the derived ultrasound image. For example, too much contrast agent will prevent the ultrasound energy from penetrating into the body, while too little agent will not be visible in the resulting image. In addition, if the rate of the contrast injection varies significantly as the ultrasound images are acquired then it is difficult to determine if the changes seen in the images are caused by actual disease or just fluctuations in injection rates. In summary, there exist three problems, which the invention described below addresses.
1. Different ultrasound responses caused by different contrast agents may cause certain features of an ultrasound machine to work incorrectly or not work at all.
2. The amount of contrast agent injected can affect the image in a detrimental way. Too much agent will not allow the ultrasound energy to penetrate into the body and too little agent will not be detectable by diagnostic ultrasound.
3. A varying injection rate of contrast agent (e.g. bolus injections) will affect the user's ability to quantify changes in the ultrasound images over time. For example, if more contrast is injected at time T1 and less contrast agent is injected at time T2, current state of the art ultrasound machines have no way of determining if the change is due to a body's anatomical function (e.g., a lack of blood flow at T2) or if the cause is a lower amount of agent.
Contrast agents are used in assessing myocardial perfusion and comprise microbubbles that are approximately the size of red blood cells or smaller and are released as a bolus or by continuous infusion into the blood stream. During subsequent imaging, the region of the myocardium with the greatest microbubble concentration appears as a region of higher intensity backscatter in the ultrasound image. This intensity decreases at a rate dependent upon the rate of perfusion through the myocardial tissue.
The relationship between the microbubble concentration and the gray level intensity of the ultrasonic image is nonlinear. The non-linearity of signal return is due, in part, to the transmit voltage level. The level of the transmit voltage, its frequency, cycle count and pulse repetition rate lead to a "contrast stability model" (hereafter referred to as "CSM"). Each CSM defines how the microbubbles react in the presence of the ultrasound signals--which reaction is a direct function of the transmit voltage. There are three known modes of CSM operation. Linear CSM is that region of transmit voltages where the contrast agent is virtually undamaged by the incident acoustic signals and occurs at low transmission voltages. The nonlinear CSM mode is that region of transmit voltages which do not instantly destroy the contrast agents, yet produce sufficiently strong acoustic signals to cause the backscatter to exhibit harmonic energies that are detectable by the ultrasound transducer. This mode occurs at medium to high transmission voltages. Lastly, the destructive CSM mode occurs at high levels of transmit power and is the region where the microbubbles are destroyed, either totally or in part.
Clearly, the relationship between the CSM mode and the transmit sequence is dependent on the type and amount of contrast agent used, variability's between patients and in the same patient, over time. Each of these variables contribute to variations in the sensed level of echo signals which make accurate quantification of the perfusion level difficult.
The prior art describes a number of methods for approaching the backscatter quantification problem. U.S. Pat. No. 5,235,984 to D'Sa, (assigned to the common assignee as this Application) describes an ultrasonic imaging system wherein selected pixel values are processed to compute an average acoustic intensity thereof. The average value is then processed to reverse any nonlinearities between the calculated average value and the originally received acoustic signals, which non-linearities may have been introduced by the processing. The processed average acoustic intensity is plotted and the procedure repeated at specified time intervals to form a time-intensity curve whose characteristics are linearly related to the originally received acoustic signals.
U.S. Pat. No. 5,063,931 to Leavitt (assigned to the same assignee as this Application) describes a method for providing gain control in a Doppler ultrasound system. The Leavitt patent teaches the generation of a training line of acoustic backscatter signals through the region of interest being imaged. Information from the backscatter that results from the training line is then utilized to maximize the gain when the scan lines are in a flow medium, while being controlled so as not to saturate the system in general. Accordingly, the same backscatter that is received from a training line within the region of interest is utilized to calibrate the return from that region of interest.
U.S. Pat. No. 5,577,505 to Brock-Fisher et al. (assigned to the same assignee as this Application) describes an ultrasound system which measures the system response under multiple excitation levels. The responses gathered from the multiple excitation levels are gain-corrected in an amount corresponding to the difference in excitation levels, and are then subtracted. Because of this subtraction, most of the linear response is removed and what remains corresponds to the nonlinear response.
U.S. Pat. No. 5,735,281 to Rafter et al. (assigned to the same assignee as this Application) is directed at resolving some of the problems created by the destruction of contrast agent microbubbles. The duration and intensity of a contrast effect is greatly diminished by conventional imaging frame rates and power levels. Altering the imaging sequence by shooting ultrasound image frames at various transmit powers and reducing the number of transmit lines per frame, allows for enhancement of the contrast effect. In effect, the Rafter et al. system enables alteration of the transmission signals to achieve the enhancement of return from a region of interest.
Additional references which speak to applications of gain control and gain assessment can be found in the following patents: U.S. Pat. No. 5,538,003 to Gadonniex et al. and U.S. Pat. No. 4,873,984 to Hunt et al., both assigned to the same assignee as this Application.
Notwithstanding the teachings of the above referenced prior art, there still remains a need for a relatively simple, real time method for enabling a quantitative assessment of tissue perfusion, when using contrast media. In addition, there is a need for a real time method of controlling the response of the contrast media to the incident ultrasound signals. Further, the method should take into account and accommodate different types of contrast agents, and variability's between patients and in a same patient, over time.